Outpatient parenteral antimicrobial therapy (OPAT) in the UK: findings from the BSAC National Outcomes Registry (2015-19).

Background: Reporting of outpatient parenteral antimicrobial therapy (OPAT) outcomes with national benchmarking is key to informing service development and supporting quality improvement.

Objectives: To analyse and report on data collected by the BSAC OPAT National Outcomes Registry from 2015 to 2019.

Methods: Quarterly data to 2020 was extracted from the BSAC National Outcomes Registry and analysed.

Namilumab or infliximab compared with standard of care in hospitalised patients with COVID-19 (CATALYST): a randomised, multicentre, multi-arm, multistage, open-label, adaptive, phase 2, proof-of-concept trial.

Background: Dysregulated inflammation is associated with poor outcomes in COVID-19. We aimed to assess the efficacy of namilumab (a granulocyte-macrophage colony stimulating factor inhibitor) and infliximab (a tumour necrosis factor inhibitor) in hospitalised patients with COVID-19, to prioritise agents for phase 3 trials.

Methods: In this randomised, multicentre, multi-arm, multistage, parallel-group, open-label, adaptive, phase 2, proof-of-concept trial (CATALYST), we recruited patients (aged ≥16 years) admitted to hospital with COVID-19 pneumonia and C-reactive protein (CRP) concentrations of 40 mg/L or greater, at nine hospitals in the UK.

CATALYST trial protocol: a multicentre, open-label, phase II, multiarm trial for an early and accelerated evaluation of the potential treatments for COVID-19 in hospitalised adults.

Introduction: Severe SARS-CoV-2 infection is associated with a dysregulated immune response. Inflammatory monocytes and macrophages are crucial, promoting injurious, proinflammatory sequelae. Immunomodulation is, therefore, an attractive therapeutic strategy and we sought to test licensed and novel candidate drugs.

Correlation between Blood and CSF Compartment Cytokines and Chemokines in Subjects with Cryptococcal Meningitis.

Background: Though peripheral blood is a crucial sample to study immunology, it is unclear whether the immune environment in the peripheral vasculature correlates with that at the end-organ site of infection. Using cryptococcal meningitis as a model, we investigated the correlation between serum and cerebrospinal fluid biomarkers over time.

Methods: We analyzed the cerebrospinal fluid and serum of 160 subjects presenting with first episode cryptococcal meningitis for soluble cytokines and chemokines measured by Luminex assay.

Case Report: Subarachnoid Hemorrhage and Eosinophilic Meningitis due to Disseminated Fascioliasis.

Human infection with the trematode occurs with a worldwide prevalence of up to 17 million. Sheep and cattle are the normal host. Infection typically results in hepatobiliary disease, but extrahepatic manifestations are occasionally reported.

Paradoxical respiratory failure due to cryptococcal pneumonia after amphotericin B treatment for HIV-associated cryptococcal meningitis.

We present a 27-year-old lady with HIV-1 infection who died due to rapidly worsening respiratory failure one day after commencing amphotericin B deoxycholate therapy for cryptococcal meningitis. Chest x-ray appearances were consistent with pneumocystis pneumonia but post mortem examination showed evidence of severe necrotizing cryptococcal pneumonia. Cryptococcal pneumonia is an underrecognized condition and should be considered in the differential of patients with HIV-1 infection and low CD4 count who develop respiratory symptoms.

Modulating host immune responses to fight invasive fungal infections.

Modulation of host immunity in invasive fungal infection is an appealing but as yet mostly elusive treatment strategy. Animal studies in invasive candidiasis and aspergillosis have demonstrated beneficial effects of colony stimulating factors, interferon-gamma and monoclonal antibodies. More recent studies transfusing leukocytes pre-loaded with lipophilic anti-fungal drugs, or modulated T-cells, along with novel vaccination strategies show great promise.

Mortality in Severe Human Immunodeficiency Virus-Tuberculosis Associates With Innate Immune Activation and Dysfunction of Monocytes.

Background: Case fatality rates among hospitalized patients diagnosed with human immunodeficiency virus (HIV)-associated tuberculosis remain high, and tuberculosis mycobacteremia is common. Our aim was to define the nature of innate immune responses associated with 12-week mortality in this population.

Methods: This prospective cohort study was conducted at Khayelitsha Hospital, Cape Town, South Africa.

The CSF Immune Response in HIV-1-Associated Cryptococcal Meningitis: Macrophage Activation, Correlates of Disease Severity, and Effect of Antiretroviral Therapy.

Background: Immune modulation may improve outcome in HIV-associated cryptococcal meningitis. Animal studies suggest alternatively activated macrophages are detrimental but human studies are limited. We performed a detailed assessment of the cerebrospinal fluid (CSF) immune response and examined immune correlates of disease severity and poor outcome, and the effects of antiretroviral therapy (ART).

A Glucuronoxylomannan-Associated Immune Signature, Characterized by Monocyte Deactivation and an Increased Interleukin 10 Level, Is a Predictor of Death in Cryptococcal Meningitis.

Background: Cryptococcal meningitis remains a significant cause of death among human immunodeficiency virus type 1 (HIV)-infected persons in Africa. We aimed to better understand the pathogenesis and identify immune correlates of mortality, particularly the role of monocyte activation.

Methods: A prospective cohort study was conducted in Cape Town, South Africa.

Flow Cytometry To Assess Cerebrospinal Fluid Fungal Burden in Cryptococcal Meningitis.

Fungal burden in the cerebrospinal fluid is an important determinant of mortality in cryptococcal meningitis, but its use in aiding clinical decision making is hampered by the time involved to perform quantitative cultures. Here, we demonstrate the potential of flow cytometry as a novel and rapid technique to address this issue.

Immune reconstitution inflammatory syndrome in HIV-infected patients.

Access to antiretroviral therapy (ART) is improving worldwide. Immune reconstitution inflammatory syndrome (IRIS) is a common complication of ART initiation. In this review, we provide an overview of clinical and epidemiological features of HIV-associated IRIS, current understanding of pathophysiological mechanisms, available therapy, and preventive strategies.

Early ART After Cryptococcal Meningitis Is Associated With Cerebrospinal Fluid Pleocytosis and Macrophage Activation in a Multisite Randomized Trial.

Introduction: Earlier antiretroviral therapy (ART) initiation in cryptococcal meningitis resulted in higher mortality compared with deferred ART initiation (1-2 weeks vs 5 weeks postmeningitis diagnosis). We hypothesized this was due to ART-associated immune pathology, without clinically recognized immune reconstitution inflammatory syndrome.

Methods: Three macrophage activation markers and 19 cytokines/chemokines were measured from cryopreserved cerebrospinal fluid (CSF) and serum during the Cryptococcal Optimal ART Timing (COAT) trial.

Household air pollution causes dose-dependent inflammation and altered phagocytosis in human macrophages.

Three billion people are exposed to household air pollution from biomass fuel use. Exposure is associated with higher incidence of pneumonia, and possibly tuberculosis. Understanding mechanisms underlying these defects would improve preventive strategies.

AIDS-related mycoses: the way forward.

The contribution of fungal infections to the morbidity and mortality of HIV-infected individuals is largely unrecognized. A recent meeting highlighted several priorities that need to be urgently addressed, including improved epidemiological surveillance, increased availability of existing diagnostics and drugs, more training in the field of medical mycology, and better funding for research and provision of treatment, particularly in developing countries.

Central nervous system immune reconstitution inflammatory syndrome.

Central nervous system immune reconstitution inflammatory syndrome (CNS-IRIS) develops in 9 %-47 % of persons with HIV infection and a CNS opportunistic infection who start antiretroviral therapy and is associated with a mortality rate of 13 %-75 %. These rates vary according to the causative pathogen. Common CNS-IRIS events occur in relation to Cryptococcus, tuberculosis (TB), and JC virus, but several other mycobacteria, fungi, and viruses have been associated with IRIS.

Management of the immune reconstitution inflammatory syndrome.

The immune reconstitution inflammatory syndrome (IRIS) is a frequent early complication of antiretroviral therapy (ART) in patients with advanced HIV. Because there is no confirmatory diagnostic test, the diagnosis is based on clinical presentation and exclusion of alternative causes for deterioration, such as antimicrobial drug resistance. Opportunistic infection treatment should be optimized.

Swine flu: a Birmingham experience.

By the beginning of July 2009 the West Midlands had seen more cases of novel H1N1 influenza (swine flu) than any other region in the U.K. Over a three-week period almost 850 people presented to Heartlands Hospital with flu-like symptoms.